Certain geranyl phenyl ethers and their epoxides and their use in controlling insects

ABSTRACT

Compounds having the formula   IN WHICH R and R1 are independently methyl or ethyl; n is the integer zero or one; R2 is hydrogen, lower alkyl, lower alkenyl, lower alkoxy, halogen, nitro, lower alkylthio, or certain hetrocyclic radicals; the use of these compounds in controlling insects; and a method of preparing certain intermediates which are useful in preparing certain of the compounds.

United States Patent [191 Pallos et al.

[ 1 Sept. 23, 1975 [22] Filed: Sept. 8, 1969 [2]] Appl. No.: 856,140

Related US. Application Data [63] Continuation-impart of Ser. No. 815,229, April 10,

. I969, abandoned.

[52] US. Cl. 260/240 II; 424/276; 424/277; 424/278; 260/327 M; 260/348 R; 260/348.5 L; 260/612 R; 260/613 D; 260/654 R [5 1] Int. Cl. C07D 303/28 [58] Field of Search 260/240 H, 348

[ 56] References Cited UNITED STATES PATENTS 3,5l3,l76 5/]970 Andrews ct al 260/240 H X 3,70l,759 l0/l972 Lee et al 3,825,602 7/1974 Pallos et al 260/609 R OTHER PUBLICATIONS Bowers et al., Science Vol. l42, pp. 1469 to M70,

Schneiderman et al., J. Insect. PhysioL, 19065, Vol. ll.pp. 1641 to 1649.

Bowers, Science, Vol, 164, pp. 323-325, (1969. April 18), relied upon as abstracted in Index Chemicus, Vol. 33, No. [14522, ('June 1969).

Primary ExaminerJohn D. Randolph Attorney, Agent, or Firm-Edwin H. Baker [57] ABSTRACT Compounds having the formula 2 CH o -1 3 in which R and R are independently methyl or ethyl; n is the integer zero or one; R is hydrogen, lower alkyl, lower alkenyl, lower alkoxy, halogen, nitro, lower alkylthio, or certain hetrocyclic radicals; the use of these compounds in controlling insects; and a method of preparing certain intermediates which are useful in preparing certain of the compounds.

20 Claims, No Drawings CERTAIN GERANYL PIIENYL ETHERS AND THEIR EPOXIDES AND THEIR USE IN CONTROLLING INSECTS which are useful in preparing certain of the novel compounds.

lt has been found that there is a class of compounds which acts in a different manner on insects than presently used insecticides and exerts a disrupting influence upon the normal development of insects. Such compounds impede the metamorphosis of the normal pupation of pest insects and result in the formation of members of the treated species which are non-viable or sterile. This ultimately leads, indirectly at least, to the destruction of a pest population.

The compounds of the present invention are believed to have the further advantages that they are non-toxic to warm-blooded animals and highly effective to control insects at low dosages. It is also hoped that it will be more difficult for insects to develop resistance against these compounds.

One embodiment of the present invention is concerned with novel pesticidal compositions.

In another embodiment, the invention is concerned with the active pesticidal component of such compositions.

In still another embodiment, the invention is concerned'with a process for controlling insects by hindering or impeding the metamorphosis and reproduction of the insects.

And in another embodiment, the'invention is concerned with a process for preparing certain epoxidized compounds.

i The compounds of the present invention that are useful in controlling insects are those having the formula in which R and R are independently methyl or ethyl, n is the integer zero or 1, preferably 1; R is hydrogen; halogen; lower alkyl having I to 6 carbon atoms, preferably l to 4 carbon atoms; lower alkoxy having 1 to 4 carbon atoms, preferably 1 to 2 carbon atoms; lower alkenyl, having 2 to 6 carbon atoms, preferably 3 to 4 carbon atoms; lower alkylthio having I to 4 carbon atoms, preferably 1 to 2 carbon atoms, nitro, or the hetrocyclic group CHR"X CHRflin which X or X" is oxygen or sulfur. CHR"-X and R", R, or R is hydrogen, methyl or ethyl; most preferably R is in the para position.

Carbon atoms, joined to two or less hydrogen atoms, occupy each angle in the backbone of the compound represented by the above formula. Letters at the terminals and branches have been used to show the attached groups.

As indicated heretofore, the above compounds are useful in impeding the metamorphosis and/or the reproduction of insects. The activity of the compounds is such that insects at any stage of their development can be effectively treated therewith.

The compound having the formula in which R, R, and R are as defined can be prepared by the following reaction:

in which R, R, and R are as defined, and X is chlorine or bromine, or iodine.

Preferably, reaction number I is carried out in a solvent such as l,2-dimethoxyethane, with stirring by slowly adding an acid acceptor, such as a diluted solution of alcoholic KOH, at room temperature, followed by heating at reflux to complete the reaction. The reaction product is recovered by conventional techniques such as stripping off the solvent in vacuum, extracting the residue with ether. washing the ether phase with 10 percent KOH solution and then with water, followed by drying with anhydrous MgSO Finally, the drying agent is filtered off and the ether is removed by vacuum stripping.

Preferably, reaction number I is carried out using equal mole amounts of the reactant, although an excess of either reactant can be used. Compounds having the in which R and R are as defined and R is as defined, excluding lower alkylthio, and said hetrocyclic group when containing a sulfur atom can be prepared by the following reaction:

. 'CH R1 .R

+ epoxidizing agent in-which R and R are as defined and R is as defined, excluding alkylthio.

Preferably, reaction number 2 is carried out in a solvent such as methylene chloride, preferably the epoxidizing agent is added slowly with stirring at a temperature sufficient to give a controlled reaction, such as about 5C. to about C. Preferably reaction number 2 is carried out using about equal mole amounts of the reactants, or with a slight excess of epoxidizing agent. The reaction product is recovered by conventional means.

The epoxidizing agents are well-known to those skilled in the art and include such materials at metachloroperbenzoic acid. Reference is made to Kirk- Othmer Encyclopedia of Chemical Technology 2nd. Edition, 1965, Vol. 8, Pages 238244, for a discussion of various types of epoxidizing agents.

Compounds having the formula in which R and R are as defined and R is lower alkylthio, or said hetrocyclic group when it contains a sulfur atom, and can be prepared by the following reactions:

agent in which R and R are as defined, and X is chlorine or bromine. or iodine, and

where either R or R are ethyl and was published by W. S. Bowers, Gordon Research Conf., June, 1968, in a symposium entitled, BIO-CHEMISTRY ANDAGRI- CULTURE, Tilton, N.H. I I Preparation of the compounds of this invention is illustrated by the following specific examples.

EXAMPLE 1 43.4 gr. (0.2 mole) geranylbromide is added to a solution of 30.0 gr. (0.22 mole) p-isopropylphenol dissolved in 220 ml. l,2-di-methoxyethane. A solution of 14.0 gr. KOH (pellets, 85 percent) in 200ml. 95percent ethanol is slowly dropped in at room temperature,

while the reaction. flask is keptin a room-temperature waterbath during the addition. A white precipitation forms and the mixture is refluxed for 2 hours. The mixtureis cooled, stripped in vacuum, and extracted with ether. The ether layer is washed twice with l0 percent KOH solution and once again with water. It is dried over anhydrous MgSO filtered, and the solvent stripped in vacuum. 41.2 gr. of a compound corresponding to the above formula is recovered having n,,"= 1.5060. The structure is confirmed by infrared and n.m.r. spectrascopy.

EXAMPLE II 7 CH CH 10.9 gr. (0.05 mole) geranylbromide is dissolved in 100 ml. methylene chloride. A stoichiometric amount I of metachloroperbenzoic acid in methylenechloride is The following is a Tableof, certain selected compounds that are preparable according to the proce- TABLE I COM- POUND NUMBER R R n R2 1 CH; CH; zero H 2 CH3 CH3 zero 4CH3 3 CH3 CH3 zero 4i-C;,H-, 4 CH3 CH3 zero 4-NO, 5 CH; CH; zero 3-Cl 6 CH3 CH5 zero 4-Cl 7 CH5 CH3 zero 4-Br 8 CH3 CH3 zero 4-! 9 C2H5 C2H,I zero 4-CH;S l CH: CH; zero 4CN l l CH, CH, zero 4sec-C H 12 CH3 CH3 zero 3-CH3O 13 CH3 CH3 zero 4-CH3O 14 CH; CH; zero 4CZH,O l C H, CH: zero 4n-C H O 16 CH 1 CH3 zero 4CH3S 17 CH3 CH3 zero 4-CH 18 CH; C2H5 zero 4i-C H, 19 CH CH; zero 4CH=CH=C(CH 2O CH3 CH; zero 4CH ,CH=CH 21 CH CH 1 H 22 CH CH 1 4-CH 23 CH CH 1 4-i-C,H, 24 CH CH 1 4--N0 25 CH CH 1 3Cl 26 CH3 CH3 1 4-Cl 27 CH CH 1 4Br 28 CH; CH, 1 4l 29 CH CH 1 4-F 30 CH CH 1 4-CN 31 CH CH 1 3-CH O- 32 CH CH 1 4-CH 0- 33 CH CH 1 4-C,H,0- 34 C,H C H 1 4- CH s- 35 CH CH 1 4n-C.H,,- 36 CH CH, 1 4-CH;,--S 37 CH CH 1 4--C H 38 CgHg, CH 1 41C;,H 39 C H, CQH; 1 4CH CH=C(CH 40 CH CH 1 4CH -CH=CH 41 CH CH 1 4-CH -CH CH(CH 42 CH; CH, 1 4nC H-, 43 CH3 CH3 0 3-CZH5 44 CH CH 1 3-C H, 45 CH CH 1 CHF CH S EXAMPLE ill dures described hereto. Compound numbers are as- CH signed to each compound and are used throughout the o 3 remainder of the spec1f1cat1on. CH INSECTICIDAL EVALUATION TEST 3 S C 3 3 The degree of activity of a candidate compound to 0.28 gr. (0.002 mole) p-(methylthio) phenol is dissolved in 3 ml. tetrahydrofuran. 2.0 ml. of a 1 mole KOH solution in 95 percent ethanol is added and 0.5 gr. (0.002 mole) of the compound prepared in Example ll, dissolved in 5 ml. tetrahydrofuranpis added. After stirring at room temperature for l hour, 30 ml. other is added, and the mixture transferred in a separatory funnel. The mixture is washed once with 10 percent Na CO solution and once with water. then dried over anhydrous MgSO... It is then filtered and stripped to yield 0.4 gr. of a compound corresponding to the above formula. The structure is confirmed by IR and n.m.r. spectrascopy.

hinder or impede the metamorphosis of insects is measured by treating the penultimate larval stage of a representative insect with the compound and examining it after its last molt toward the adult form for retention of immature features.

Specifically, hellow mealworm. 'I'enebriu mulimr. L.. larvae are maintained at 28C. and 40 percent humidity on a diet of bran flakes. Prepupae are collected from the culture and kept in separate containers. The pupae collected once daily, are l-25 hours old at the time of treatment. By means of a syringe, suitable amounts of candidate compounds in 0.5 or 1.0 p.l of acetone are applied to the venter of Tenebrio molitor, L. pupae. Treated pupae are maintained at 28C. and 40 percent humidity until the adults emerged (usually within 6-8 days). Emerged adults are graded as positive, negative; or dead. To be considered a positive response, the pres ence of typical pupal cuticle, urogomphi, gin trap, and abnormal wings, etc. are 'required. For each test, 2

groups ofpupae were used-and the averaged results 5 were reported.

The dose of: a candidatecompou nd per-pupa that is needed to kill or givea positive response in the above 'termined. Table ,lI shows these doses under the column TABLE I1 COMPOUND NUMBER ED -ug/pupa The compounds of this invention are generally embodied into a form suitable for convenient application. For example, the compounds can be embodied into. pesticidal composition which are provided in the form of emulsions, suspensions. solutions, dusts, and aerosol sprays. In general, such compositions will contain, in addition to the active compound, the adjuvants which are found normally in pesticide preparations. In these compositions, the active compounds of this invention can be employed as the sole pesticide component or they can be used in admixture with other compounds having similar utility. The pesticide compositions of this invention can contain. as adjuvants, organic solvents, such as sesame oil. xylene range solvents. heavy petroleum, etc.; water; emulsifying agents; surface active agents; talc; pyrophyllite; diatomite; gypsum; clays; propellants, such as dichlorodifluoromethane. etc. If' desired, however, the active compounds can be applied directly to feedstuffs, seeds, ctc. upon which the pests feed. When applied in such a manner. it will be advantageous to use a compound which is not volatile. In connection with-the activity of the presently disclosed i that it is not necessary that they be active as such. The

purposes of this invention will be fully'served if the compound is rendered active by external influences. such as light or by some physiological action which occurs when the compound is ingested into the body of v the pest.

1nsect1c1dal evaluatlon test for 10 of the 20 pupae 15 de- A preclbe manner m which the pestle compo tions of this invention are used in any particular instance will be readily apparent to a person skilled in the art. Generally, the active pesticide compound will be embodied in the form of a liquid composition, for example, an emulsion, suspension, or aerosol spray. While the concentration of the active pesticide in the present compositions can vary within rather wide limits, ordinarily the pesticide compound will comprise not more than about 15.0 percent by weight of the composition. Preferably, however, the pesticide compositions of this invention will be in the form of solutions or suspensions containing about O.l to 1.0 percent by weight of the active pesticide compound.

What is claimed:

l. A compound of the formula:

in which R and R are independently methyl or ethyl; R is hydrogen; halogene; lower alkyl having I to 6 carbon atoms; lower alkoxy having I to 4 carbon atoms; lower alkcnyl having 2 to 6 carbon atoms; lower alkylthio having I to 5 carbon atoms; or nitro.

2. The compound of claim I in which R and R are methyl; and R is lower alkyl having 1 to 4 carbon atoms;

' 3. The compound of claim 1 in which R and R are methyl; and R is lower alkoxy having 1 to 2 carbon atoms;

4. The compound of claim 1 in which R and R' are methyl; and R is lower alkylthio having l to 2 carbon atoms.

5. The compound of claim 1 in which R and R are methyl; and R is halogen.

6. The compound of claim 2 in which R is 4-methyl.

7 The compound, of claim 2 in which R is 4-i-propyl.

8. The compound of claim 3 in which R is 4- methoxy. I

9. The compound of, claim 4 in which R is 4- methylthio.

10. The compound of claim 2 in which R is 4 ethyl.

11. The compound of claim 1 in which R and R are ethyl; and R is lower alkyl having 1 to 4 carbon atoms.-

12. The compound of claim"! in which R and R are ethyl; and R islowe r alkoxy having l to 2 carbon atoms.

1.3. The compound of claim l in which R and R' are ethyl; and R atoms. '7

is lower alkylthio having I to 2 carbon l4. The compound of claim 1 in which R and R are ethyl; and R is halogen.

15. The compound of claim 11 in which R is 4- 18. The compound of claim 13 in which R 4- methylthio.

19. The compound of claim 11 in which R is 4-ethyl. 20. A compound of the formula wherein R is selected from the group consisting of [0 lower alkyl, lower alkoxy and halo. 

1. A COMPOUND OF THE FORMULA:
 2. The compound of claim 1 in which R and R1 are methyl; and R2 is lower alkyl having 1 to 4 carbon atoms.
 3. The compound of claim 1 in which R and R1 are methyl; and R2 is lower alkoxy having 1 to 2 carbon atoms.
 4. The compound of claim 1 in which R and R1 are methyl; and R2 is lower alkylthio having 1 to 2 carbon atoms.
 5. The compound of claim 1 in which R and R1 are methyl; and R2 is halogen.
 6. The compound of claim 2 in which R2 is 4-methyl.
 7. The compound of claim 2 in which R2 is 4-i-propyl.
 8. The compound of claim 3 in which R2 is 4-methoxy.
 9. The compound of claim 4 in which R2 is 4-methylthio.
 10. The compound of claim 2 in which R2 is 4-ethyl.
 11. The compound of claim 1 in which R and R1 are ethyl; and R2 is lower alkyl having 1 to 4 carbon atoms.
 12. The compound of claim 1 in which R and R1 are ethyl; and R2 is lower alkoxy having 1 to 2 carbon atoms.
 13. The compound of claim 1 in which R and R1 are ethyl; and R2 is lower alkylthio having 1 to 2 carbon atoms.
 14. The compound of claim 1 in which R and R1 are ethyl; and R2 is halogen.
 15. The compound of claim 11 in which R2 is 4-methyl.
 16. The compound of claim 11 in which R2 is 4-i-propyl.
 17. The compound of claim 12 in which R2 is 4-methoxy.
 18. The compound of claim 13 in which R2 is 4-methylthio.
 19. The compound of claim 11 in which R2 is 4-ethyl.
 20. A compound of the formula 